The mu, or morphine preferring, opiate receptor is the receptor most identified with the addictive and analgesic properties of opiate drugs. Previous studies with antagonists have identified regulation of receptor binding properties and/or function following chronic opiate administration. For these reasons, the regional distribution and regulated expression of rat mu opiate receptor (muOR) mRNA and protein, and regulation of this expression, are of interest. Regional distribution assessment using a ribonuclease protection assay revealed that the most abundant muOR mRNA was found in thalamus, followed by hypothalamus, midbrain, and spinal cord. This mRNA was also detected in cortex, striatum, brainstem, hippocampus, but not in cerebellum or peripheral tissues. In situ hybridization studies revealed that subpopulations of neurons in several thalamic nuclei express muOR mRNA, with most abundant expression in neurons of the medial aspect of the lateral habenula. Developmental studies detected muOR mRNA in brains from embryos as early as 14 days gestation. In cerebral cortex, these levels plateaued after birth. In mesencephalon, pons and medulla, however, postnatal development continued to reach expression levels more than 2-fold higher at 6 weeks that at the end of the first week of life. Withdrawal from chronic morphine treatments showed modest effects on rat brain muOR mRNA levels that did not reach statistical significance. These studies begin to reveal some of the exquisitely detailed regulated expression of this principal receptor for rewarding and analgesic actions of opiate drugs.